Human pain and genetics: some basics

Abstract

Human pain causes untold misery and suffering, with major impact on functioning and resources. Recent advances in genetics have revealed that subtle changes in DNA could partly explain the variation in individual differences in pain. Various genes encoding for receptors are now known to play a major role in the sensitivity, perception and expression of pain. The fields of epigenetics and proteomics hold promises in the way pain could be treated and managed in future.

Keywords

Chronic pain fibromyalgia hereditary sensory and autonomic neuropathies musculoskeletal pain nociceptive pain genetics pain post-operative pain insensitivity congenital pain perception temporomandibular joint dysfunction syndrome

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References

Young

Lariviere

Belfer

. Genetic basis of pain variability. J Med Genet 2012; 49(1): 1–19.

Faucett

Gordon

Levine

. Differences in postoperative pain severity among four ethnic groups. J Pain Symptom Manage 1994; 9: 383–389.

Fillingim

. Sex, gender and pain: women and men really are different. Curr Rev Pain 2000; 4: 24–30.

Dorner

Muckenhuber

Stronegger

. The impact of socio-economic status on pain and the perception of disability due to pain. Eur J Pain 2011; 15: 103–109.

Diatchenko

Slade

Nackley

. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 2005; 14: 135–143.

Lacroix-Fralish

Mogil

. Progress in genetic studies of pain and analgesia. Annu Rev Pharmacol Toxicol 2009; 49: 97–121.

A haplotype map of the human genome. The International HapMap Consortium. Nature 2005; 437: 1299–1320.

Venter

Adams

Myers

. The sequence of the human genome. Science 2001; 291: 1304–1351.

Devor

. Chapter 23. What are pain genes and why are they interesting? In: Mogil

(ed.) Pain (An updated review). Seattle, WA: IASP Press, 2010, pp. 227–237.

10.

Norbury

MacGregor

Urwin

. Heritability of responses to painful stimuli in women: a classical twin study. Brain 2007; 130: 3041–3049.

11.

Williams

Spector

MacGregor

. Pain reporting at different body sites is explained by a single underlying genetic factor. Rheumatology (Oxford) 2010; 49: 1753–1755.

12.

Catterwall

. Overview of the voltage-gated sodium channel family. Genome Biol 2003; 4: 207.

13.

Wang

Y-Q

. Are voltage-gated sodium channels on the dorsal root ganglion involved in the development of neuropathic pain? Mol Pain 2011; 7: 16.

14.

De vries

Frants

Ferrari

. Molecular genetics of migraine. Hum Genet 2009; 126: 115–132.

15.

Drenth

Waxman

. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. J Clin Invest 2007; 117: 3603–3609.

16.

Hoeijmakers

Faber

Lauria

. Small-fiber neuropathies – advances in diagnosis, pathophysiology and management. Nat Rev Neurol 2012; 8: 369–379.

17.

Faber

Hoeijmakers

Ahn

. Gain-of-function mutation in idiopathic small fiber neuropathy. Ann Neurol 2012; 71: 26–39.

18.

Faber

Lauria

Merkies

ISJ

. Gain-of-function Na_v1.8 mutations in painful neuropathy. Proc Natl Acad Sci U S A 2012; 109(47): 19444–19449.

19.

Duan

Xiang

Zhang

. A single nucleotide polymorphism in SCN9A may decrease postoperative pain sensitivity in the general population. Anesthesiology 2013; 118(2): 436–442.

20.

Cox

Reimann

Nicholas

. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006; 444: 894–898.

21.

Nagasako

Oaklander

Dworkin

. Congenital insensitivity to pain: an update. Pain 2003; 101: 213–219.

22.

Dib-Hajj

Rush

Cummins

. Gain-of-function mutation in Na_v1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain 2005; 128: 1847–1854.

23.

Fertleman

Ferrie

Aicardi

. Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology 2007; 69: 586–595.

24.

D’Mello

Dickenson

. Spinal cord mechanisms of pain. Br J Anaesth 2008; 101: 8–16.

25.

Diatchenko

Nackley

Tchivileva

. Genetic architecture of human pain perception. Trends Genet 2007; 23: 605–613.

26.

Tegeder

Adolph

Schmidt

. Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase 1 haplotype. Eur J Pain 2008; 12: 1069–1077.

27.

Lotsch

Klepstad

Doehring

. A GTP cyclohydrolase 1 genetic variant delays cancer pain. Pain 2010; 148: 103–106.

28.

Amaya

Wang

Costigan

. The voltage-gated sodium channel Na_v1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci 2006; 26: 12852–12860.

29.

Chang

Arendt-Nielsen

Graven-Nielsen

. Psychophysical and EEG responses to experimental muscle pain in humans: pain intensity encodes EEG activity. Brain Res Bull 2003; 59: 533–543.

30.

Buskila

. Genetics of chronic pain states. Best Pract Res Clin Rheumatol 2007; 21: 535–547.

31.

Zubieta

Smith

Bueller

. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 2001; 293: 311–315.

32.

Nackley

Tan

Fecho

. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta-2 and beta-3-adrenergic receptors. Pain 2007; 128: 199–208.

33.

Hocking

Smith

Jones

. Genetic variation in the beta2-adrenergic receptor, but not COMT predisposes to chronic pain: results from the 1958 British Birth Cohort Study. Pain 2010; 149: 143–151.

34.

Tegeder

Costigan

Griffin

. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 2006; 12: 1269–1277.

35.

Ichinose

Suzuki

Inagaki

. Molecular genetics of dopa-responsive dystonia. Biol Chem 1999; 380: 1355–1364.

36.

Oertel

Lotsch

. Genetic mutations that prevent pain: implications for future pain medication. Pharmacogenetics 2008; 9(2): 179–194.

37.

Reyes-Gibby

Shete

Rakvag

. Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain 2007; 130: 25–30.

38.

Angst

Koppert

Pahl

. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain 2003; 106: 49–52.

39.

Joly

Richebe

Guignard

. Remifentanil-induced post-operative hyperalgesia and its prevention with small dose ketamine. Anesthesiology 2005; 103: 147–155.

40.

Guo

Liu

Zhang

. Association between Caspase-9 promoter region polymorphisms and discogenic back low back pain. Connect Tissue Res 2011; 52: 133–138.

41.

Binder

May

Baron

. Transient receptor potential channel polymorphism are associated with the somatosensory function in neuropathic pain patients. PLoS One 2011; 6(3): e17387.

42.

Gan

Lin

Zhang

. Association of an interleukin-16 gene polymorphism with the risk and pain phenotype of endometriosis. DNA Cell Biol 2010; 29: 663–667.

43.

Denk

McMahon

. Chronic pain: emerging evidence for the involvement of epigenetics. Neuron 2012; 73: 435–444.

44.

Buchheit

Van de Ven

Shaw

. Epigenetics and the transition from acute to chronic pain. Pain Med 2012; 13: 1474–1490.

45.

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. The Wellcome Trust Case Control Consortium. Nature 2007; 447: 661–678.

46.

Tegeder

Lotsch

. Current evidence for a modulation of low back pain by human genetic variants. J Cell Mol Med 2009; 13(88): 1605–1619.

47.

Nissenbaum

. From mouse to humans: discovery of the CACNG2 pain susceptibility gene. Clin Genet 2012; 82: 311–320.

48.

Rebsamen

Desmeules

Daali

. The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction. Pharmacogenomics J 2009; 9: 34–41.

49.

Goldberg

Price

Namdari

. Treatment of Na_v1.7 mediated pain in inherited erythromelalgia using a novel sodium channel blocker. Pain 2012; 153: 80–85.

50.

Beutler

Reinhardt

. AAV for pain: steps towards clinical translation. Gene Ther 2009; 16: 461–469.

51.

Handy

Krudy

Boulis

. Gene therapy: a potential approach for cancer pain. Pain Res Treat 2011; 2011: Article ID 987597 (12 pp.).

52.

Wolfe

Matta

Fink

. A human trial of HSV mediated gene transfer for the treatment of chronic pain. Gene Ther 2009; 16(4): 455–460.

53.

Fink

Wechuck

Mata

. Gene therapy for pain: results of a phase I clinical trial. Ann Neurol 2011; 70(2): 207–212.

54.

Clinical Trial.govIdentifier: NCT01291901.

55.

Franchi

Valsecchi

Borsani

. Intravenous neural stem cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy. Pain 2012; 153: 850–861.